[-(2,4-dimethoxybenzyloxycarbamoyl)-2-hydroxy-ethyl]carbamic acid tert-butyl ester | 501701-41-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [-(2,4-dimethoxybenzyloxycarbamoyl)-2-hydroxy-ethyl]carbamic acid tert-butyl ester
• CAS: 501701-41-3
• 化学式: C₁₇H₂₆N₂O₇
• 分子量: 370.403
• InChiKey: QWJBCVFMWXCYNK-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.14
• 重原子数：
  26.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  115.35
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  [-(2,4-dimethoxybenzyloxycarbamoyl)-2-hydroxy-ethyl]carbamic acid tert-butyl ester 在 吡啶 、 2,6-二甲基吡啶 、 三氟甲磺酸三甲基硅酯 、 polystyrene tosyl chloride resin 、 三乙胺 作用下， 以 吡啶 、 二氯甲烷 为溶剂， 反应 25.67h， 生成 (R)-2-(3-Fluoro-5-trifluoromethyl-phenyl)-4,5-dihydro-oxazole-4-carboxylic acid (2,4-dimethoxy-benzyloxy)-amide
  参考文献：
  名称：

  High-Throughput Catch-and-Release Synthesis of Oxazoline Hydroxamates. Structure−Activity Relationships in Novel Inhibitors of Escherichia coli LpxC:  In Vitro Enzyme Inhibition and Antibacterial Properties

  摘要：

  LpxC is a zinc amidase that catalyses the second step of lipid A biosynthesis in Gram-negative bacteria. Oxazolines incorporating a hydroxamic acid, which is believed to coordinate to the single essential zinc ion, at the 4-position are known inhibitors of this enzyme. Some of these enzyme inhibitors exhibit antibacterial activity through their inhibition of LpxC. We recently developed a method for the synthesis of oxazolines using resin capture and ring-forming release that eliminates traditional purification steps and can be used in high-throughput synthesis. Using our method, oxazoline hydroxamates with diverse 2-substituents were prepared in library form as candidate inhibitors for LpxC. Two conventional methods for oxazoline synthesis were also applied to generate more than 70 compounds. The groups at the 2-position included a wide variety of substituted aromatic rings and a limited selection of alkyl groups. These compounds were screened against wild-type and LpxC inhibitor-sensitive strains of Escherichia coli, as well as wildtype Pseudomonas aeruginosa. Inhibition of the E coli LpxC enzyme was also investigated. A broad correlation between enzyme inhibitory and antibacterial activity was observed, and novel compounds were discovered that exhibit antibacterial activity but fall outside earlier-known structural classes.

  DOI：

  10.1021/ja0209114
• 作为产物：
  描述：

  2,4-二甲氧基苄醇 在 三丁基膦 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 甲基肼 、 偶氮二甲酸二乙酯 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 25.0h， 生成 [-(2,4-dimethoxybenzyloxycarbamoyl)-2-hydroxy-ethyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  High-Throughput Catch-and-Release Synthesis of Oxazoline Hydroxamates. Structure−Activity Relationships in Novel Inhibitors of Escherichia coli LpxC:  In Vitro Enzyme Inhibition and Antibacterial Properties

  摘要：

  LpxC is a zinc amidase that catalyses the second step of lipid A biosynthesis in Gram-negative bacteria. Oxazolines incorporating a hydroxamic acid, which is believed to coordinate to the single essential zinc ion, at the 4-position are known inhibitors of this enzyme. Some of these enzyme inhibitors exhibit antibacterial activity through their inhibition of LpxC. We recently developed a method for the synthesis of oxazolines using resin capture and ring-forming release that eliminates traditional purification steps and can be used in high-throughput synthesis. Using our method, oxazoline hydroxamates with diverse 2-substituents were prepared in library form as candidate inhibitors for LpxC. Two conventional methods for oxazoline synthesis were also applied to generate more than 70 compounds. The groups at the 2-position included a wide variety of substituted aromatic rings and a limited selection of alkyl groups. These compounds were screened against wild-type and LpxC inhibitor-sensitive strains of Escherichia coli, as well as wildtype Pseudomonas aeruginosa. Inhibition of the E coli LpxC enzyme was also investigated. A broad correlation between enzyme inhibitory and antibacterial activity was observed, and novel compounds were discovered that exhibit antibacterial activity but fall outside earlier-known structural classes.

  DOI：

  10.1021/ja0209114